VA Researchers Identify Biomarkers for Possible ‘Suicidality Blood Test’

By Brenda L. Mooney

INDIANAPOLIS, IN — What if it were possible to identify veterans at risk for suicide through a simple blood test?

Research from the Richard L. Roudebush VAMC in Indianapolis and Indiana University School of Medicine suggests that concept might not be as far-fetched as it may seem. A report, published online recently by the journal Molecular Psychiatry, said researchers have identified a series of RNA biomarkers in blood that might help single out who is at risk for taking their own lives.1

Those biomarkers were found at significantly higher levels in the blood of both bipolar disorder patients with suicide ideation as well in a group of people who had committed suicide. “Overall, suicidality may be underlined, at least in part, by biological mechanisms related to stress, inflammation and apoptosis,” according to the study authors.

“As the target organ in psychiatry — the brain — cannot be biopsied in live patients, it is essential to be able to identify and validate peripheral biomarkers for subsequent practical implementation in clinical settings,” they added. “We now present a comprehensive and highly reductionist approach for discovering and validating blood biomarkers for suicidality.”

The results provide a first “proof of principle” for a test to help healthcare providers at the VA and elsewhere determine who was at higher risk for an impulsive act such as suicide, said principal investigator Alexander B. Niculescu III, MD, PhD of the Indianapolis VAMC.

“Suicide is a big problem in psychiatry. It’s a big problem in the civilian realm, it’s a big problem in the military realm, and there are no objective markers,” Niculescu said. “There are people who will not reveal they are having suicidal thoughts when you ask them, who then commit it, and there’s nothing you can do about it. We need better ways to identify, intervene and prevent these tragic cases.”

Alexander B. Niculescu III, MD, PhD

For the study, Niculescu and his colleagues followed a large group of patients diagnosed with bipolar disorder — many of them war veterans receiving care at the Indianapolis VAMC. The researchers interviewed the study participants and took blood samples every three to six months over a three-year period.

When analyzing blood of a subset of participants who reported a dramatic shift from no suicidal thoughts to strong suicidal ideation, the investigators were able to identify differences in gene expression between the “low” and “high” states of suicidal thoughts. Those findings then were cross-validated with other lines of evidence to find and prioritize the best markers.

Biological Signal

The marker spermidine/spermine N1–acetyltransferase 1 (SAT1) and, to a lesser extent, a series of other markers provided the strongest biological “signal” associated with suicidal thoughts, according to the researchers. In an effort to validate the results, blood samples from known suicide victims were obtained from a local coroner’s office and compared with the study samples. The researchers found that some of same top markers were significantly elevated.

Analyzing blood test results from two additional groups of patients, investigators found that high blood levels of the biomarkers were correlated with future suicide-related hospitalizations, as well as hospitalizations that had occurred before the blood tests.

“This suggests that these markers reflect more than just a current state of high risk but could be trait markers that correlate with long-term risk,” Niculescu pointed out.

Blood levels of SAT1, which was the the top biomarker identified at the time of testing, appeared to be linked to future as well as past hospitalizations with suicidality, in the bipolar disorder subjects. A similar but weaker pattern was exhibited in a live cohort of subjects with schizophrenia/schizoaffective disorder, according to the authors.

Three other biomarkers — phosphatase and tensin homolog (PTEN), myristoylated alanine-rich protein kinase C substrate (MARCKS), and mitogen-activated protein kinase kinase kinase 3 (MAP3K3) — showed similar effects, but less strongly.

“Taken together, the prospective and retrospective hospitalization data suggests SAT1, PTEN, MARCKS and MAP3K3 might be not only state biomarkers but trait biomarkers as well,” the authors wrote.

Niculescu said he was confident in the biomarkers’ validity but pointed to some of the study’s limitations, including that all subjects were male.

“There could be gender differences,” Niculescu said. “We would also like to conduct more extensive, normative studies, in the population at large.”

Nonetheless, he added. “These seem to be good markers for suicidal behavior in males who have bipolar mood disorders or males in the general population who commit impulsive violent suicide. In the future we want to study and assemble clinical and socio-demographic risk factors, along with our blood tests, to increase our ability to predict risk.”

He suggested that blood biomarkers, along with other tools, including neuropsychological tests and socio-demographic checklists currently in development by his group, ultimately can be used to help identify those at risk for suicide, enabling healthcare providers to intervene.

“Suicides are a leading cause of death in psychiatric patients, and in society at large. Developing more quantitative and objective ways [biomarkers] for predicting and tracking suicidal states would have immediate practical applications and positive societal implications,” the study authors wrote.

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  1. Le-Niculescu H, Levey DF, Ayalew M, Palmer L, Discovery and validation of blood biomarkers for suicidality. Mol Psychiatry. 2013 Aug 20. doi: 10.1038/mp.2013.95. [Epub ahead of print] PubMed PMID: 23958961.

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